Central mediation of the antihypertensive effect of pargyline in spontaneously hypertensive rats.

Abstract

The monoamine oxidase (MAO) inhibitor pargyline induced a moderate (about 20 mm Hg) but persistent (48 h) decrease of systolic blood pressure in unanesthetized adult spontaneously hypertensive rats (SHR) but not in normotensive rats. The fall of blood pressure correlated with the blockade of norepinephrine (NE) deamination by brain homogenates. After an intracerebroventricular (icv) injection of 6-hydroxydopamine, which lowered brain NE content by about 70%, pargyline was unable to diminish arterial pressure. Blockade of central alpha-adrenoceptors by treatment with phentolamine (100 microgram icv) could either prevent or reverse the fall of blood pressure in SHR induced by pargylline. Moreover, a low dose of pargyline injected directly into the brain lowered arterial pressure. We conclude that the hypotensive action of pargylline in SHR appears to be the consequence of NE accumulating at an inhibitory alpha-adrenoceptor in brain.